A new scientific review raises key questions about how diet—and especially carbohydrate intake—could enhance or hinder the impact of GLP-1 receptor agonists.
The rise of GLP-1 drugs like semaglutide and tirzepatide has transformed the treatment landscape for obesity and type 2 diabetes. Yet, behind the headlines, real-world effectiveness remains uneven. Why do some patients succeed and others struggle? A recent review published in Nutrients by Zanoni et al. (2024) suggests that diet composition, microbiome balance, and insulin dynamics may be part of the answer.
The Missing Link: Gut Microbiota and Macronutrients
The authors explore how GLP-1 is not just an injected molecule—it is also a natural hormone secreted by the gut, tightly regulated by what we eat. In particular, glucose and insulin signaling play a major role in GLP-1 dynamics. So does the gut microbiota, which can either enhance or blunt the body’s response to GLP-1 through complex interactions involving bile acids, short-chain fatty acids, and inflammatory markers.
Low-Carb and Ketogenic Diets: A Strategic Leverage?
One of the central points in the review is that reducing dietary carbohydrate intake—especially refined carbohydrates—may improve GLP-1 responsiveness. The authors reference studies where ketogenic or very-low-carb diets (under 50 g/day) not only reduce insulin resistance but also restore endogenous GLP-1 secretion and support beneficial shifts in the gut microbiota.
Key mechanisms include:
- Lower glucose spikes = reduced glucotoxicity = improved GLP-1 sensitivity
- Higher fat intake = enhanced bile acid signaling = microbiome reshaping
- Reduced insulin = lower systemic inflammation = better metabolic outcomes
In this model, the drug and the diet reinforce each other: the GLP-1 agonist reduces appetite and promotes satiety, while the diet reduces metabolic noise and inflammation—amplifying the drug’s effects.
Why Lifestyle Still Matters in the GLP-1 Era
GLP-1 therapies are powerful tools—but they don’t override physiology. Without adapting nutrition and lifestyle, weight regain, side effects, and early discontinuation remain common. This review highlights how specific dietary strategies, such as fiber modulation, carbohydrate reduction, and ketogenic patterns, could directly support the pharmacological action of GLP-1.
This is where boli begins
At boli, we believe GLP-1 drugs are only part of the solution. To unlock their full potential, patients need science-backed, behaviorally realistic, and metabolically targeted guidance.
Our digital therapeutic program supports patients not only in managing GLP-1 side effects, but also in adopting a nutrition strategy that improves their metabolic baseline. That often means reducing carbohydrate intake, increasing protein and fiber, and progressively building a personalized threshold for metabolic balance.
Because in the end, the injection is not the intervention—metabolic care is.
Reference:
Zanoni, S., Berti, A., Ferrulli, A., & Scacchi, M. (2024). Nutritional and Microbiota-Related Effects on Glucagon-like Peptide-1 Action: A Review on Mechanisms and Clinical Implications. Nutrients, 17(16), 2699. https://doi.org/10.3390/nu17162699
